{"doi":"10.7554/elife.109257","title":"Profiling of terminating ribosomes reveals translational control at stop codons","abstract":"Accurate termination of protein synthesis is paramount for the integrity of the cellular proteome, yet the dynamics and fidelity of ribosome termination remain poorly understood. Here, we establish a profiling strategy to capture terminating ribosomes in mammalian cells and reveal a substantial heterogeneity in ribosome pausing at individual stop codons. We identify a sequence motif upstream of the stop codon that promotes termination pausing, a finding supported by massively parallel reporter assays. Unexpectedly, reduced termination pausing increases the likelihood of stop codon slippage, giving rise to proteins with heterogeneous C-terminal extensions. Mechanistically, we show that sequence-dependent termination pausing is consistent with post-decoding mRNA scanning by the 3' end of 18 S rRNA. We further uncover tissue-specific patterns of termination pausing that correlate with the stoichiometry of Rps26, which potentially modulates mRNA:rRNA interactions. Together, these results suggest termination pausing as a distinct translational signature shaped by mRNA sequence contexts, ribosome heterogeneity, and cell type-specific translational control.","journal":"eLife","year":2025,"id":581178,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE270879"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":54471,"name":"Yuanhui Mao","orcid":"0000-0002-0893-2588","position":1,"is_corresponding":false},{"id":1023188,"name":"Saori Uematsu","orcid":"0000-0002-7033-9494","position":2,"is_corresponding":false},{"id":1492837,"name":"Xinyi Ashley Liu","orcid":null,"position":3,"is_corresponding":false},{"id":1492510,"name":"Leiming Dong","orcid":"0000-0003-0111-3720","position":4,"is_corresponding":false},{"id":1492511,"name":"Leonardo Henrique França de Lima","orcid":"0000-0003-4346-9880","position":5,"is_corresponding":false},{"id":425647,"name":"Shu‐Bing Qian","orcid":"0000-0002-4127-1136","position":6,"is_corresponding":false},{"id":233250,"name":"Longfei Jia","orcid":"0009-0004-1852-5857","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:58:47.357782Z","pmid":"42412910","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}